Biomedical subjects

Cesare Manetti

Publications and source records attributed to Cesare Manetti.

9 recordsLinked to original sources

PubMed2006

A metabonomic study of transgenic maize (Zea mays) seeds revealed variations in osmolytes and branched amino acids.

The aim of the research was to investigate metabolic variations associated with genetic modifications in the grains of Zea mays using metabonomic techniques. With this in mind, the non-targeted characteristic of the technique is useful to identify metabolites peculiar to the genetic modification and initially undefined. The results obtained showed that the genetic modification, introducing Cry1Ab gene expression, induces metabolic variations involving the primary nitrogen pathway. Concerning the methodological aspects, the experimental protocol used has been applied in this field for the first time. It consists of a combination of partial least square-discriminant analysis and principal component analysis. The most important metabolites for discrimination were selected and the metabolic correlations linking them are identified. Principal component analysis on selected signals confirms metabolic variations, highlighting important details about the changes induced on the metabolic network by the presence of a Bt transgene in the maize genome.

Amino Acids, Branched-Chain↗

PubMed2005

Early events in protein aggregation: molecular flexibility and hydrophobicity/charge interaction in amyloid peptides as studied by molecular dynamics simulations.

In a previous article (Zbilut et al., Biophys J 2003;85:3544-3557), we demonstrated how an aggregation versus folding choice could be approached considering hydrophobicity distribution and charge. In this work, our aim is highlighting the mutual interaction of charge and hydrophobicity distribution in the aggregation process. Use was made of two different peptides, both derived from a transmembrane protein (amyloid precursor protein; APP), namely, Abeta(1-28) and Abeta(1-40). Abeta(1-28) has a much lower aggregation propensity than Abeta(1-40). The results obtained by means of molecular dynamics simulations show that, when submitted to the most "aggregation-prone" environment, corresponding to the isoelectric point and consequently to zero net charge, both peptides acquire their maximum flexibility, but Abeta(1-40) has a definitely higher conformational mobility than Abeta(1-28). The absence of a hydrophobic "tail," which is the most mobile part of the molecule in Abeta(1-40), is the element lacking in Abeta(1-28) for obtaining a "fully aggregating" phenotype. Our results suggest that conformational flexibility, determined by both hydrophobicity and charge effect, is the main mechanistic determinant of aggregation propensity.

Amyloid↗

PubMed2005

LF-NMR and multivariate data analysis: compression of data to classify hydrogel contact lenses.

Hydrogel contact lenses swollen in viscoelastic artificial tears solution have been studied, measuring transversal relaxation times of water molecules using LF-NMR techniques. Data were processed by classical multiexponential fitting, by principal component analysis and by SLICING, a multi-way analysis method. The reason for using multivariate data analysis was not to obtain a better fitting, but rather more effective data description. The single-sample relaxation curves were projected in a space spanned by the loading curves, and in this space it was simpler to compare data. In particular, it contributed to the description of the variability of motion characteristics of the water molecule 'families' contained in the studied samples. Applying multivariate techniques, we were able to group lenses with different Equilibrium Water Content (EWC) and with the same water content but different compositions. Accordingly, we were able to point out that, if the lenses are swollen first in physiological solution and then in viscoelastic artificial tears solution, hydration characteristics remained unchanged in all the studied samples, except for 38% EWC lenses.

Algorithms↗

PubMed2004

Application of trilinear SLICING to analyse a single relaxation curve.

Determining the time constants and amplitudes of exponential decays from relaxation data is a common task in LF-NMR. In this communication, we present an application of the SLICING algorithm to evaluate its possibilities for solving this problem. The method, originally introduced to compare different samples, is applied here to analyse a single relaxation curve, using the embedding technique. To test this procedure, we acquired data sets from samples of liquids properly separated, and characterized by different relaxation times. The results show a good estimation of parameters, comparable with those obtained applying Marquardt's algorithm, when the components have sufficiently different relaxation times.

Journal Article↗

PubMed2004

NMR-based metabonomic study of transgenic maize.

The aim of this research was to verify the possibility of identifying and classifying maize seeds obtained from transgenic plants, in different classes according to the modification, on the basis of the concerted variation in metabolite levels detected by NMR spectra. It was possible to recognise the discriminant metabolites of transgenic samples as well as to classify non-a priori defined samples of maize. It is important to underline that the obtained results are useful to point out the metabolic consequences of a specific genic modification on a plant, without using a targeted analysis of the different metabolites, in fact it was possible to classify the seeds also without the complete assignment of the spectra. The analysis was performed by applying multivariate techniques (principal component analysis and partial least squares-discriminant analysis) to NMR data.

Gene Expression↗

PubMed2004

LF-NMR water self-diffusion and relaxation time measurements of hydrogel contact lenses interacting with artificial tears.

The different swelling properties of ionic and non-ionic lenses, immersed in sodium chloride or artificial tears, were investigated by Low-Field Nuclear Magnetic Resonance (LF-NMR) through relaxation time and self-diffusion coefficient measurements. A new model was developed to estimate the water self-diffusion coefficient inside the lenses, the results of which revealed a different mechanism of interaction for ionic versus non-ionic materials with artificial tears. The consequence of this finding suggests clinical implications.

Contact Lenses↗

PubMed2003

Protein aggregation/folding: the role of deterministic singularities of sequence hydrophobicity as determined by nonlinear signal analysis of acylphosphatase and Abeta(1-40).

The problem of protein folding vs. aggregation was investigated in acylphosphatase and the amyloid protein Abeta(1-40) by means of nonlinear signal analysis of their chain hydrophobicity. Numerical descriptors of recurrence patterns provided the basis for statistical evaluation of folding/aggregation distinctive features. Static and dynamic approaches were used to elucidate conditions coincident with folding vs. aggregation using comparisons with known protein secondary structure classifications, site-directed mutagenesis studies of acylphosphatase, and molecular dynamics simulations of amyloid protein, Abeta(1-40). The results suggest that a feature derived from principal component space characterized by the smoothness of singular, deterministic hydrophobicity patches plays a significant role in the conditions governing protein aggregation.

Acid Anhydride Hydrolases↗

PubMed2002

(13)C-NMR isotopomer distribution analysis: a method for measuring metabolic fluxes in condensation biosynthesis.

(13)C NMR spectroscopy associated with the use of (13)C-enriched substrates is a powerful tool to investigate intracellular metabolism because of the wealth of information contained in the distribution of isotopes in key metabolites. A new method of using (13)C label distribution measurements in carbon skeletons of metabolites to estimate metabolic fluxes through biochemical reaction networks is presented here. This method can be applied to metabolite synthesis occurring by condensation reactions of the type nA --> B, where n is the number of precursor A molecules needed to synthesize one molecule of product B. NMR isotopomer distribution analysis (NMR-IDA) involves the introduction of a (13)C-enriched precursor, and measurements of the (13)C positional enrichments at just one carbon atom position of the product B via (13)C NMR spectroscopy. Information on isotopomer distribution is obtained, and data are analyzed according to a mathematical model based on multinomial probability expressions to obtain the best fit between theoretical and experimental (13)C label distribution. The use of the NMR-IDA method allows for estimation of two key parameters representing the fractional flux of (13)C-enriched tracer A molecules to total precursor A pool and the fraction of product B synthesized in the presence of a (13)C-enriched source, respectively. A practical example of NMR-IDA application to fatty acid synthesis from [(1,2 (13)C(2))acetyl]-L-carnitine in cultured primary astrocytes is also presented.

Animals↗

PubMed2002

Review of nonlinear analysis of proteins through recurrence quantification.

This review considers the use of a nonlinear signal analysis tool, recurrence quantification analysis, as a method to study sequence/structure relationships of proteins. Four broad categories are discussed: (1) a point of view involving information contained in deterministic aspects of hydrophobicity; (2) the analysis of protein hydrophobicity "singularities"; (3) time-series analysis of protein dynamics simulations; and (4) prediction of protein secondary structure.

Algorithms↗